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Biomedical subjects

D M Foster

Publications and source records attributed to D M Foster.

At least 19 recordsLinked to original sources
PubMed1992

Protein transfer between A-I-containing lipoprotein subpopulations: evidence of non-transferable A-I in particles with A-II.

Transfer of apolipoproteins (apo) between the two subpopulations of apo A-I-containing lipoproteins in human plasma: those with A-II [Lp(AI w AII)] and those without [Lp(AI w/o AII)], were studied by observing the transfer of 125I-apo from a radiolabeled subpopulation to an unlabeled subpopulation in vitro. When Lp(AI w AII) was directly radioiodinated, 50.3 +/- 7.4 and 19.5 +/- 7.7% (n = 6) of the total radioactivity was associated with A-I and A-II, respectively. In radioiodinated Lp(AI w/o AII), 71.5 +/- 6.8% (n = 6) of the total radioactivity was A-I-associated. Time-course studies showed that, while some radiolabeled proteins transferred from one population of HDL particles to another within minutes, at least several hours were necessary for transfer to approach equilibrium. Incubation of the subpopulations at equal A-I mass resulted in the transfer of 51.8 +/- 5.0% (n = 4) of total radioactivity from [125I]Lp(AI w/o AII) to Lp(AI w AII) at 37 degrees C in 24 h. The specific activity (S.A.) of A-I in the two subpopulations after incubation was nearly identical. Under similar incubation conditions, only 13.4 +/- 4.6% (n = 4) of total radioactivity was transferred from [125I]Lp(AI w AII) to Lp(AI w/o AII). The S.A. of A-I after incubation was 2-fold higher in particles with A-II than in particles without A-II. These phenomena were also observed with iodinated high-density lipoproteins (HDL) isolated by ultracentrifugation and subsequently subfractionated by immunoaffinity chromatography. However, when Lp(AI w AII) radiolabeled by in vitro exchange with free [125I]A-I was incubated with unlabeled Lp(AI w/o AII), the S.A. of A-I in particles with and without A-II differed by only 18% after incubation. These data are consistent with the following: (1) in both populations of HDL particles, some radiolabeled proteins transferred rapidly (minutes or less), while others transferred slowly (hours); (2) when Lp(AI w AII) and Lp(AI w/o AII) were directly iodinated, all labeled A-I in particles without A-II were transferable, but some labeled AI in particles with A-II were not; (3) when Lp(AI w AII) were labeled by in vitro exchange with [125I]A-I, considerably more labeled A-I were transferable. These observations suggest the presence of non-transferable A-I in Lp(AI w AII).

Adult↗
PubMed1992

Psyllium husk. I: Effect on plasma lipoproteins, cholesterol metabolism, and atherosclerosis in African green monkeys.

Psyllium's effects on plasma and lipoprotein cholesterol concentrations, cholesterol metabolism, and diet-induced atherosclerosis were studied in adult male African green monkeys (Cercopithecus aethiops). Animals were fed for 3.5 y one of three experimental diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). The LCC and HCP groups had significantly (P less than 0.05) lower plasma cholesterol concentrations (39% lower) at 1 mo than did the HCC group. These responses persisted throughout the study. Plasma cholesterol changes were due to a reduction in intermediate-density and low-density lipoproteins; very-low and high-density-lipoprotein concentrations were similar among groups. Aortic atherosclerosis, evaluated as percent sudanophilia at 3.5 y, was lowest in the LCC group, intermediate in the HCP group, and highest in the HCC group. Cholesterol absorption, neutral steroid and fat excretion, HMGCoA reductase activity (in intestine and liver), and body weight were unrelated to psyllium's hypocholesterolemic effects.

Animals↗
PubMed1992

Psyllium husk. II: Effect on the metabolism of apolipoprotein B in African green monkeys.

Dietary psyllium's ability to reduce low-density-lipoprotein (LDL) cholesterol is presumably mediated by increased LDL catabolism and/or reduced LDL synthesis. To distinguish between these possibilities, apolipoprotein B (apo B) metabolism was studied in adult male African green monkeys consuming one of three semipurified diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). 131I-labeled LDL and 125I-labeled VLDL were injected simultaneously into animals; blood samples were drawn at selected times and apo B specific activity determined in VLDL, IDL, and LDL. Based on a multicompartmental model, LDL apo B pool size and de novo apo B transport were elevated significantly in HCC animals compared with HCP and LCC animals. Differences in LDL transport, although not significant, paralleled differences observed in LDL apo B pool size. Fractional catabolic rates were similar among groups (HCC 0.040 +/- 0.010; HCP 0.042 +/- 0.009, and LCC 0.043 +/- 0.004 pools/h). These data suggest that dietary psyllium reduces plasma cholesterol concentrations by decreasing LDL synthesis.

Animals↗
PubMed1992

Tracer-to-tracee ratio for analysis of stable isotope tracer data: link with radioactive kinetic formalism.

A kinetic formalism for the analysis of stable isotope transient tracer data is developed by establishing the link with the formalism available for radioactive tracer data. The crucial variable is the tracer-to-tracee ratio. By expressing the measurements in terms of this ratio, the conventional kinetic formalism used for radioactive data can be applied to estimate noncompartmental parameters using stable isotope tracer data. The tracer-to-tracee ratio also plays an important role in compartmental modeling. By considering the tracer masses in the compartments as state variables the system-experiment model can be written in a format analogous to that usually adopted for the radioactive tracer. Finally, it is shown that the tracer-to-tracee ratio also plays a role in a test of the endogenous steady-state assumption.

Animals↗
PubMed1991

Metabolic regulation of plasma apolipoprotein E by estrogen and progesterone in the baboon (Papio sp).

Apolipoprotein (apo) E plays an important role in the metabolism of lipoproteins. To determine the effects of estrogen and progesterone on plasma levels and metabolism of apo E, we used 12 ovariectomized baboons fed a cholesterol- and fat-enriched diet. These baboons were divided into four groups and treated with estrogen, progesterone, estrogen + progesterone, and a placebo control. After 10 months, although the lipid levels were not different among the treatment groups, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratios in the estrogen + progesterone group were significantly lower than those in the control and progesterone groups. Estrogen alone or in combination with progesterone decreased plasma apo E levels significantly compared with those in the control group. Plasma apo E levels in the progesterone group were similar to those in the control group. In all groups, most (greater than 60%) of the apo E was present in HDL. HDL apo E concentrations in the estrogen and estrogen + progesterone groups were significantly lower than those in the control and progesterone groups. To determine the metabolic mechanisms of these changes in apo E levels, turnover studies were conducted by injection of iodinated apo E-labeled very-low-density lipoprotein (VLDL) and HDL. Residence times were calculated using multicompartment modeling. Progesterone alone and in combination with estrogen decreased residence times of apo E injected in both HDL and VLDL compared with estrogen alone and control groups. Progesterone alone also increased the apo E production rate compared with other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Enhancement of antibody production by lysophosphatidylcholine and alkylglycerol.

Inflammation products of normal and cancerous tissues, lysophosphatidylcholine and dodecylglycerol, were tested for their adjuvant effect on the antibody response. Mice treated with these agents and immunized with sheep erythrocytes simultaneously or at 3 days posttreatment developed a greatly enhanced antibody production as demonstrated by the Jerne plaque assay. Mice immunized at 3 days postadministration of agents did not significantly produce enhanced antibody-secreting cells as compared with those of mice simultaneously immunized. Since the mechanism of macrophage activation by lysophospholipids requires contribution of B and T cells, BALB/c-nu/nu mice treated with these agents and subsequently immunized with sheep erythrocytes did not produce antibodies. However, conditioned medium of in vitro-treated BALB/c-nu/nu B cells efficiently transmitted a signal to untreated BALB/c +/+ T cells for enhanced macrophage ingestion activity. This observation suggests that lysophospholipid-activated macrophages and T cells efficiently transmitted antigenic signal to the antibody-producing B cell population. Therefore, we conclude that these lipid metabolites have dual beneficial effects for the host by enhancing phagocytosis and antibody production. Thus, lysophosphatidylcholine and dodecylglycerol have potential practical application as adjuvants that could be administered separately or in combination with antigens.

Animals↗
PubMed1990

Metabolic regulation of apoproteins of high-density lipoproteins by estrogen and progesterone in the baboon (Papio sp).

To determine the metabolic regulation of the apoproteins of high-density lipoproteins (HDL) by estrogen and progesterone, 12 ovariectomized and hysterectomized baboons were fed a high cholesterol, high fat diet and were divided into four groups. One of these groups was the untreated control and the remaining three groups were treated with estrogen, progesterone, or a combination of both. After 10 months of treatment, there were significant differences in HDL apolipoprotein (apo) A-I and apo A-II levels in these groups. The apo A-I level was highest in baboons treated with the combination therapy, followed by those treated with estrogen. Baboons treated with progesterone and those in the control group had similar levels of apo A-I. Baboons treated with both estrogen and progesterone and estrogen alone had significantly higher levels of apo A-I than those in the control or progesterone group. Baboons treated with hormones had higher apo A-II levels than controls, and those treated with the combination therapy had the highest level. Metabolic studies suggested that both estrogen and progesterone increased apo A-I and apo A-II production. Progesterone also increased the fractional catabolic rate of apo A-I, but not of apo A-II. On the other hand, estrogen did not affect the fractional catabolic rate of either apo A-I or apo A-II. Thus, increased apo A-I content of HDL in baboons treated with both estrogen and progesterone or estrogen alone appears to be due to increased apo A-I synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of estrogen and progesterone on metabolism of apoprotein B in baboons.

To determine the metabolic mechanisms by which estrogen and progesterone alter levels of apoprotein B (apo B)-containing lipoproteins, 12 ovariectomized and hysterectomized baboons, maintained on a high-cholesterol (1.7 mg/kcal) and a high-fat (40% from lard) diet and divided into four groups, were treated with estrogen, progesterone, estrogen plus progesterone, and a placebo. After 12 wk, plasma cholesterol was unchanged in the control and progesterone groups but was reduced in the estrogen- and estrogen plus progesterone-treated groups. The reduction was primarily because of decreased low-density lipoprotein (LDL) cholesterol. LDL apo B levels decreased parallel to the LDL cholesterol. Very low-density lipoprotein (VLDL) and LDL apo B metabolism were studied using a double-label turnover study. Multicompartmental modeling suggested that LDL apo B was kinetically heterogeneous and that there exists an extravascular pool, perhaps consisting of hepatic remnants, that contributes significantly to LDL apo B transport. The model was used to estimate apo B production rates and residence times. VLDL apo B production was not affected by estrogen but was increased by progesterone. LDL apo B production was increased by both estrogen and progesterone. The residence time of LDL apo B was decreased by estrogen and estrogen plus progesterone but not by progesterone. Thus estrogen and progesterone have independent effects on apo B metabolism in baboons.

Animals↗
PubMed1990

Hepatic apo B-100 lipoproteins and plasma LDL heterogeneity in African green monkeys.

The contribution of hepatic apolipoprotein (apo) B-100 lipoproteins to plasma low-density lipoprotein (LDL) metabolic heterogeneity was examined in African green monkeys. Hepatic 3H-labeled very low-density lipoproteins (VLDL) (d less than 1.006, where d is density in g/ml) or hepatic 131I-labeled LDL (1.030 less than d less than 1.063) were isolated from perfused livers and injected simultaneously with autologous plasma 125I-LDL into African green monkeys. Serial blood samples were taken, and the distribution of radioactivity among various subfractions of apo B-100 lipoproteins was determined using density-gradient ultracentrifugation. Compartmental models were developed to describe simultaneously the kinetics of hepatic lipoproteins and plasma LDL. In five of seven studies, the metabolic behavior of LDL derived from radiolabeled hepatic lipoprotein precursors differed from the metabolic behavior of radiolabeled autologous plasma LDL. These differences could be described by different models supporting two hypotheses with different physiological interpretations: 1) lipoproteins of donor and recipient animals are kinetically distinct, and/or 2) plasma LDL derived from various potential sources are kinetically distinct. Compartmental modeling was used to test these hypotheses, which were not accessible to testing by conventional experimental methodologies. The kinetic analyses of these studies suggest that plasma LDL may be derived from a variety of precursors, including hepatic VLDL and hepatic LDL, with each source giving rise to metabolically distinct plasma LDL.

Animals↗
PubMed1990

Effects of fish oil on VLDL triglyceride kinetics in humans.

Dietary n-3 fatty acids (FAs) found in fish oils markedly lower plasma triglyceride (TG) and very low density lipoprotein (VLDL) levels in both normal and hypertriglyceridemic subjects. The present study examined the mechanism of this effect. Ten subjects with widely different plasma triglyceride levels (82 to 1002 mg/dl) were fed metabolically controlled diets containing 20% fat. The control diet contained a blend of cocoa butter and peanut oil (P/S = 0.8). The test diet contained fish oil (P/S = 1.1) and provided 10-17 g of n-3 FAs per day (depending on calorie intake). After 3 to 5 weeks of each diet, the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol. The fish oil diet reduced the VLDL-TG synthetic rate from 23 +/- 14.3 (mean +/- SD) to 12.6 +/- 7.5 mg/h per kg ideal weight (P less than 0.005) and increased the fractional catabolic rate (FCR) for VLDL-TG from 0.23 +/- 0.12 to 0.38 +/- 0.16 h -1 (P less than 0.005). At the same time, there was a 66% reduction of plasma triglyceride levels, resulting largely from a 78% decrease in VLDL-TG levels (398 +/- 317 to 87 +/- 77 mg/dl; P less than 0.005). There was a strong correlation (r = 0.83; P less than 0.01) between the change in synthetic rates and pool sizes, but there was no correlation (r = 0.24; NS) between changes in FCRs and pool sizes. The VLDL cholesterol: triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present. These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR. We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis, but an additional, independent effect upon VLDL catabolism cannot be ruled out.

Dietary Fats, Unsaturated↗
PubMed1990

Conversion of plasma VLDL and IDL precursors into various LDL subpopulations using density gradient ultracentrifugation.

The contribution of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) to various low density lipoprotein (LDL) subfractions was examined in three normal subjects and two with familial combined hyperlipidemia. Autologous VLDL + IDL (d less than 1.019 g/ml) or VLDL only (d less than 1.006 g/ml; one subject only) were isolated by sequential ultracentrifugation, iodinated, and injected into each subject. The appearance, distribution, and subsequent disappearance of radioactivity into LDL density subpopulations was characterized using density gradient ultracentrifugation. These techniques help determine the contribution of precursors to various LDL subpopulations defined uniquely for each subject. The results from these studies have suggested: 1) it took up to several days of intravascular processing of precursor-derived LDL before it resembled the distribution of the 'steady-state' plasma LDL protein; 2) plasma VLDL and IDL precursors contributed rapidly to a broad density range of LDL; 3) the radiolabeled plasma precursors did not always contribute to all LDL density subfractions within an individual in proportion to their relative LDL protein mass as determined by density gradient ultracentrifugation; 4) with time, the distribution of the precursor-derived LDL became more buoyant or more dense than distribution of the LDL protein mass; and 5) the kinetic characteristics of precursor-derived particles within LDL changed within a relatively narrow density range and were not always related to the LDL density heterogeneity of each subject. These studies emphasize the complexities of apoB metabolism and the need to design studies to carefully examine the production of various LDL subpopulations, the kinetic fate and interconversions among the subpopulations, and ultimately, their relationship to the development of atherosclerosis.

Apolipoproteins B↗
PubMed1989

A resource facility for kinetic analysis: modeling using the SAAM computer programs.

Kinetic analysis and integrated system modeling have contributed significantly to understanding the physiology and pathophysiology of metabolic systems in humans and animals. Many experimental biologists are aware of the usefulness of these techniques and recognize that kinetic modeling requires special expertise. The Resource Facility for Kinetic Analysis (RFKA) provides this expertise through: (1) development and application of modeling technology for biomedical problems, and (2) development of computer-based kinetic modeling methodologies concentrating on the computer program Simulation, Analysis, and Modeling (SAAM) and its conversational version, CONversational SAAM (CONSAM). The RFKA offers consultation to the biomedical community in the use of modeling to analyze kinetic data and trains individuals in using this technology for biomedical research. Early versions of SAAM were widely applied in solving dosimetry problems; many users, however, are not familiar with recent improvements to the software. The purpose of this paper is to acquaint biomedical researchers in the dosimetry field with RFKA, which, together with the joint National Cancer Institute-National Heart, Lung and Blood Institute project, is overseeing SAAM development and applications. In addition, RFKA provides many service activities to the SAAM user community that are relevant to solving dosimetry problems.

Animals↗
PubMed1989

Metabolism of larger high density lipoproteins accumulating in some families of baboons fed a high cholesterol and high saturated fat diet.

Progeny of certain baboon sires accumulate lipoproteins in high density lipoprotein-1 (HDL1) when challenged with a high cholesterol, high saturated fat diet. These studies were conducted to determine the apoprotein composition and metabolic fate of HDL1 in the plasma. HDL1 particles containing apoA-I with and without apoE were detected. The majority of particles, however, contained apoA-I without any detectable apoE. To determine the metabolic fate of HDL1 in plasma, HDL1 labeled with iodinated apoA-I from animals with high levels of HDL1 and iodinated apoA-I-labeled autologous HDL were coinjected into both high and low HDL1 animals. The data for the decay of radioactivity in HDL1 and HDL were analyzed by multicompartment modelling. The radioactivity from HDL1 was cleared from the plasma either via direct removal (9.1 +/- 4.7% in low and 21.7 +/- 8.3% in high HDL1 animals) or via its conversion to HDL. A large proportion of radioactivity from HDL1 was rapidly transferred to HDL directly or metabolized via an intermediate compartment. Most of the radioactivity from apoE-poor HDL1, however, was transferred to HDL. Both high and low HDL1 animals catabolized HDL1 and HDL similarly. Low HDL1 animals transferred HDL1 radioactivity to HDL much faster. No detectable radioactivity from HDL was transferred to HDL1. Thus, HDL1 that accumulates in high HDL1 animals is mainly a precursor for HDL. Our hypothesis is that this accumulation of HDL1 is due to the slower cholesteryl ester transfer from HDL to lower density lipoproteins, thus affecting reverse cholesterol transport in high HDL1 baboons.

Animals↗
PubMed1989

Relationships between LDL density and kinetic heterogeneity in subjects with normolipidemia and familial combined hyperlipidemia using density gradient ultracentrifugation.

The metabolism of heterogeneous subpopulations of low density lipoprotein (LDL) apoB100 was examined in three normolipidemic and two familial combined hyperlipidemic subjects. Autologous radioiodinated plasma LDL (1.019 less than d less than 1.063 g/ml) were injected into each subject and the disappearance and appearance of radiolabeled lipoproteins into various LDL subpopulations were examined using density gradient ultracentrifugation. Eleven to 13 fractions (-320 microliter each) were collected within LDL defined uniquely in each subject. In all subjects, the disappearance of radiolabeled LDL from plasma was biexponential. However, changes with time in the distribution of radiolabeled LDL among the various LDL density subpopulations revealed complex metabolic behavior that differed among the subjects. When the relationships between density and kinetic characteristics were examined in more detail by following the disappearance of individual fractions defining LDL in each subject, the data suggested that: 1) the kinetic behavior of the LDL fractions was more complex than suggested by the disappearance of radiolabeled LDL from plasma: 2) certain fractions within specific density ranges were kinetically similar; 3) distinct differences in the disappearance curves among the fractions occurred within narrow density ranges; and 4) precursor-product relationships were seen among specific LDL density fractions and varied from subject to subject. These studies underscore the complexities of plasma LDL apoB-100 metabolism. More detailed characterizations of the kinetic behavior of various LDL subpopulations should help in our understanding of the origin(s) and potential physiological consequences of different LDL subpopulations.

Adult↗
PubMed1989

Metabolic behavior of hepatic VLDL and plasma LDL apoB-100 in African green monkeys.

Recently, evidence has accumulated suggesting that significant amounts of plasma low density lipoproteins (LDL) may be derived by direct production. These plasma very low density lipoprotein (VLDL)-independent sources include the production and secretion of LDL-like particles directly by the liver, and/or a small pool of nascent precursor particles that are converted rapidly to LDL. The current studies were designed to test the hypothesis that hepatic VLDL represent a rapidly turning over precursor pool to plasma LDL in African green monkeys. Livers from African green monkeys were perfused with serum-free medium containing [3H]leucine or 3H-labeled amino acids for 4-6 hr. Hepatic [3H]VLDL and autologous plasma 125I-labeled LDL were injected simultaneously into recipient animals and density gradient ultracentrifugation and gel filtration were used to characterize the distribution of 3H and 125I radioactivity at selected times after injection. These studies show that 4 to 66% of the injected dose of hepatic VLDL [3H]apoB-100 was metabolized extremely rapidly into particles that resembled the recipient's plasma LDL by size and density. Based on the kinetic model developed to describe the metabolic behavior of hepatic VLDL [3H]apoB-100, the estimated maximal pool size of hepatic VLDL apoB-100 in these animals was very small (0.042 and 0.112 mg) and represented, at best, approximately 10% of the average plasma VLDL apoB-100 mass found in cholesterol-fed African green monkeys. In addition, the radiolabeled hepatic LDL appear to be metabolized similarly to plasma LDL. That is, the rapid conversion of hepatic VLDL as well as the direct production of hepatic particles within the LDL density range appear to contribute to plasma LDL. Metabolic heterogeneity was also seen within the LDL class. The more buoyant subfraction (LDL1) had a higher turnover rate than the more dense subfraction (LDL2) and hepatic VLDL-derived [3H]LDL1 had a slower final rate of plasma disappearance than the plasma-derived 125I-labeled LDL1 in most animals. The results from these studies suggest that a small pool of hepatic VLDL can be converted very rapidly to plasma LDL and may contribute significantly to the large plasma pool of LDL seen in cholesterol-fed African green monkeys. This pathway may be analogous to the pathway in some human subjects in which a portion of human plasma VLDL is converted rapidly into LDL without passing through a delipidation cascade, often referred to as direct LDL production.

Animals↗
PubMed1988

Applications of a general method for deconvolution using compartmental analysis.

A method of deconvolution is illustrated using compartmental models. The approach can be used to determine an arbitrary unknown input function from a measured response and the impulse response of the system. Compartmental models are constructed to specify (a) the function fitting the response data and (b) the impulse response of the system. Simulation of these models is then used to construct the unknown input function.

Alanine↗
PubMed1987

Metabolic consequences of genetic heterogeneity of lipoprotein composition (lipoprotein heterogeneity).

Lipoprotein composition varies among different genetic forms of hyperlipidemia. An increase in hepatic triglyceride (TG) synthesis in subjects with familial hypertriglyceridemia (FHTG) is associated with secretion of large, TG-enriched, very low-density lipoproteins (VLDL), which have an increased affinity for lipoprotein lipase (LPL) in vivo as compared with VLDL from subjects with familial combined hyperlipidemia (FCHL) or from normal subjects. Elevated levels of plasma low-density lipoprotein (LDL) apoprotein B in FCHL are associated with high apoprotein B production rates. The LDL in FCHL is heterogeneous, with a preponderance of an LDL subfraction, which is denser, smaller, and lipid poor as compared with LDL from normal subjects. The more buoyant LDL subfraction in FCHL seems to be catabolized more rapidly than this dense LDL subfraction.

Apolipoproteins B↗